Copyright © 2004, European Society of Cardiology
Role of different proton-sensitive channels in releasing calcitonin gene-related peptide from isolated hearts of mutant mice
aDepartment of Physiology and Experimental Pathophysiology, Friedrich-Alexander-University of Erlangen-Nuremberg, Universitätsstr. 17, D-91054 Erlangen, Germany
bCenter of Cardiac Surgery, Friedrich-Alexander-University of Erlangen-Nuremberg, Krankenhausstr. 12, D-91054 Erlangen, Germany
* Corresponding author. Tel.: +49 9131 852 2228; fax: +49 9131 852 2497. Email address: reeh{at}physiologie1.uni-erlangen.de
Objective: Calcitonin gene-related peptide (CGRP), a potent vasodilator released from a subset of sensory A
- and C-fiber afferents, has been suggested to play a beneficial role in myocardial ischemia. The aim of the present study was to investigate some receptors possibly involved in the proton-mediated CGRP release from the heart.
Methods: CGRP release from freshly isolated hearts of mice lacking the capsaicin receptor (TRPV1–/–), the bradykinin receptor type 2 (B2–/–), or the acid-sensing ion channel type 3 (ASIC3–/–) and their wild-type littermates (TRPV1+/+, B2+/+, ASIC3+/+) were compared. Hearts were passed through a series of solutions based on oxygenated synthetic interstitial fluid (SIF). SIF buffered to pH 5.7 or 5.2 was used as an acidic test stimulus, and capsaicin (5 x 10–7 M) was finally applied as a positive control. All eluates were processed using an enzyme immunoassay (EIA) for measurement of CGRP concentrations.
Results: SIF at pH 5.7 and 5.2 caused significant increases in CGRP release in TRPV1+/+ but not in mice lacking the TRPV1 receptor. The same acid stimuli caused no significant differences in CGRP release between ASIC3+/+ and ASIC3–/– or between B2+/+ and B2–/–, respectively. Capsaicin caused massive CGRP release in all mouse genotypes with the exception of TRPV1–/–.
Conclusion: We conclude that cardiac acidosis is a strong stimulus to release CGRP from the mouse heart. This effect seems to be primarily mediated through activation of TRPV1 receptors that are known to be expressed by slowly conducting nociceptive primary afferent nerve fibers.
KEYWORDS Heart; Ischemia; CGRP release; TRPV1; ASIC3; Bradykinin receptor
Time for primary review 16 days
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